Prostrate cancer impairs (mostly) old men's life and sexuality. Surgery leaves them impotent in most of the cases, as penile nerves are touched. Recently, a team at the University of Southern California has developed a prostate cancer vaccine impeding the development of cancer in 90% of young mice engineered to grow the cancer. The research published in "Cancer Research" shows this vaccine could rise in men the amounts of PSA (prostate specific antigen), an indicator of prostate cancer.

"By early vaccination, we have basically given these mice life-long protection against a disease they were destined to have. This has never been done before and, with further research, could represent a paradigm shift in the management of human prostate cancer," said lead researcher Dr. W. Martin Kast, a professor of Molecular Microbiology & Immunology and Obstetrics & Gynecology, at the Norris Comprehensive Cancer Center.

"Now, men with rising PSA levels but no other signs of cancer are advised 'watchful waiting' - no treatment until signs of the cancer appear. But what if instead of a watchful wait, we vaccinate. Vaccines now in testing are designed to treat men whose cancers are advanced and unresponsive to therapy, and results have offered limited clinical benefit. This novel approach targets the precancerous state with the aim of preventing cancer from developing," said Kast.

The new preventive vaccine triggers an immune response against prostate stem cell antigen (PSCA), a membrane protein targeted also by other trialled therapeutic vaccines.

PSCA is over-expressed in about 30% of early-stage prostate cancers, but this is boosted in all developing prostate cancers. Low levels of PSCA are present in healthy prostate gland tissue, but also in the bladder, colon, kidney and stomach. The new strategy would include, in fact, two types of vaccines, checked in 8-week-old engineered mice.

The first vaccine contained a DNA patch encoding for PSCA, delivering an influx of PSCA that sensitized the immune cells to this protein. The booster shot was delivered two weeks later and employed a mutated horse virus containing the PSCA gene.
"Confronting the immune system in two different ways forces it to mount a strong response," said Kast.

2 of 20 vaccinated mice developed prostate cancer until the end of one year, while all control individuals died of prostate cancer. All vaccinated mice had developed tiny stable tumors.

"There were tiny nodules of prostate cancer in the mice that were surrounded by an army of immune system cells. The vaccination turned the cancer into a chronic, manageable disease. The vaccination strategy also works with other antigens," said Kast.

Another vaccine developed by the same team targeted another prostate cancer membrane and discovered that after 1.5 years, 65% of vaccinated mice were still alive, while the others died because of the old age (the lifespan of mice is 1.5-2 years). Moreover, vaccinated mice did not develop autoimmune disease, an undesired effect that could target PSCA expression in healthy cells.

"Theoretically, the vaccine could produce a response in any tissue that expresses the antigen, but the fact that PSCA is expressed in such low levels in normal tissue may prevent that complication. Still, studies in humans are needed to ensure autoimmunity does not develop. We feel this is a very promising approach. With just two shots, the vaccine will prime immune cells to be on the lookout for any cell that over-expresses PSCA," said Kast.